Interpretive Handbook

Test
8411 :
Adrenocorticotropic Hormone (ACTH), Plasma

Adrenocorticotropic hormone (ACTH), the primary stimulator of adrenal cortisol production, is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH), which is released by the hypothalamus. Plasma ACTH and cortisol levels exhibit peaks (6-8 a.m.) and nadirs (11 p.m.).

Cortisol, the main glucocorticoid, plays a central role in glucose metabolism and in the body's response to stress. Only a small percentage of circulating cortisol is biologically active (free form), with the majority of cortisol inactive (protein bound). Cortisol is inactivated in the liver and excreted in the urine as conjugated compounds (largely 17-hydroxysteroids). Urine free cortisol levels reflect circulating free plasma cortisol levels.

In a patient with hypocortisolism, an elevated adrenocorticotropic hormone (ACTH) indicates primary adrenal insufficiency, whereas a value that is not elevated is consistent with secondary adrenal insufficiency from a pituitary or hypothalamic cause.

In a patient with hypercortisolism (Cushing syndrome), a suppressed value is consistent with a cortisol-producing adrenal adenoma or carcinoma, primary adrenal micronodular hyperplasia, or exogenous corticosteroid use.

Normal or elevated ACTH in a patient with Cushing syndrome puts the patient in the ACTH-dependent Cushing syndrome category. This is due to either an ACTH-producing pituitary adenoma or ectopic production of ACTH (bronchial carcinoid, small cell lung cancer, others). Further diagnostic studies such as dexamethasone suppression testing, corticotropin-releasing hormone stimulation testing, petrosal sinus sampling, and imaging studies are usually necessary to define the ACTH source.

In very rare instances of the ectopic adrenocorticotropic hormone (ACTH) syndrome, the elevated ACTH may be biologically active but not detected by the immunometric assay.

Patients taking glucocorticoids may have suppressed levels of ACTH with an apparent high level of cortisol. This may be due to cross-reactivity with the cortisol immunoassays. If exogenous Cushing is suspected, a cortisol level determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (eg, COR / Cortisol, Serum, LC-MS/MS) should be used with the ACTH level for the interpretation.